Homoharringtonine Compared With Hydroxyurea for Chronic Myelogenous Leukemia That Has Not Responded to Interferon Alfa
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if homoharringtonine is more effective than hydroxyurea for chronic myelogenous leukemia that has not responded to interferon alfa.
PURPOSE: Randomized phase III trial to compare the effectiveness of homoharringtonine with that of hydroxyurea in treating patients who have chronic myelogenous leukemia that has not responded to interferon alfa.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: hydroxyurea Drug: Homoharringtonine |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase III Study of Interferon-Refractory Patients With BCR/ABL(+) Chronic Myelogenous Leukemia (CML) Treated With Homoharringtonine (NSC #141633) vs. Hydroxyurea |
- Overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
| Enrollment: | 5 |
| Study Start Date: | January 2000 |
| Primary Completion Date: | May 2001 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Homoharringtonine |
Drug: Homoharringtonine
2.5 mg/ sq m/ day CIVI for 14 days
|
| Active Comparator: Hydroxyurea |
Drug: hydroxyurea
0.5 to 5 grams PO per day
|
Detailed Description:
OBJECTIVES: I. Compare the overall survival of interferon alfa refractory chronic myelogenous leukemia patients treated with homoharringtonine to those treated with hydroxyurea. II. Compare the time to progression of these patients treated with these two drugs. III. Estimate the complete and major cytogenetic response and describe the serial cytogenetics of these patients treated with these two drugs.
OUTLINE: This is a randomized study. Patients are randomized to receive one of two treatments. Arm I: Induction: Patients receive homoharringtonine IV continuously over 24 hours daily for 14 days. Induction continues every 28 days for a maximum of 6 courses or until hematopoietic recovery. Maintenance: Patients receive homoharringtonine IV continuously over 24 hours daily for 5 days. Treatment repeats every 28 days. Arm II: Induction: Patients receive oral hydroxyurea daily for 28 days until acceptable blood counts are achieved. Maintenance: Patients receive oral hydroxyurea daily every 28 days to maintain acceptable blood counts. Treatment in both arms continues for a minimum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for a maximum of 10 years.
PROJECTED ACCRUAL: A total of 480 patients (240 per arm) will be accrued for this study within 4 years.
Eligibility| Ages Eligible for Study: | 16 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Cytologically proven chronic phase chronic myelogenous leukemia Philadelphia chromosome detectable by cytogenetic studies OR 1 of the following: BCR/ABL protein detectable by immunoblotting BCR/ABL rearrangement detectable by Southern blot analysis Polymerase chain reaction positive fusion transcripts for BCR/ABL BCR/ABL translocation present by fluorescence in situ hybridization No prior intolerance or failure to respond to hydroxyurea Must have failed adequate trial (5M units/m2/day) of interferon alfa (IFN) or the combination of IFN and cytarabine as defined by 1 of the following: Failure to achieve complete hematologic response after 6 months of IFN Failure to achieve any cytogenetic response (i.e., still 100% Philadelphia chromosome positive) after 12 months of IFN Intolerable adverse effects of IFN after at least 1 month of IFN Significant documented toxicity of grade 3 or greater due to IFN required Loss of a prior hematologic remission or cytogenetic response to IFN Two-fold increase in WBC count compared to WBC count when IFN initiated
PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified Cardiovascular: No uncontrolled tachyarrhythmias (e.g., atrial fibrillation, paroxysmal superventricular tachycardia, or ventricular tachycardias not adequately controlled) Other: Not pregnant or nursing Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 7 days since prior interferon alfa Chemotherapy: See Disease Characteristics No prior homoharringtonine Less than 180 days cumulative prior hydroxyurea No more than 60 days hydroxyurea after failing interferon Endocrine therapy: No concurrent hormones except for nondisease related conditions (e.g., insulin for diabetes, estrogen for osteopenia) Concurrent steroids for adrenal failure allowed Radiotherapy: No concurrent palliative radiotherapy Surgery: No concurrent splenectomy except for emergency management
Contacts and Locations
Show 133 Study Locations| Study Chair: | Meir Wetzler, MD | Roswell Park Cancer Institute |
| Study Chair: | Harry P. Erba, MD, PhD | University of Michigan Cancer Center |
More Information
No publications provided
| Responsible Party: | Monica M Bertagnolli, Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00004933 History of Changes |
| Other Study ID Numbers: | CDR0000067617, U10CA031946, CLB-19807, SWOG-C19807 |
| Study First Received: | March 7, 2000 |
| Last Updated: | August 1, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Cancer and Leukemia Group B:
|
relapsing chronic myelogenous leukemia chronic phase chronic myelogenous leukemia Philadelphia chromosome positive chronic myelogenous leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Homoharringtonine Hydroxyurea Interferons Harringtonines Antineoplastic Agents Therapeutic Uses |
Pharmacologic Actions Antisickling Agents Hematologic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Antiviral Agents Anti-Infective Agents Antineoplastic Agents, Phytogenic Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013